mortality/aging
• 50% mortality around 7 weeks of age and 100% mortality by 10 weeks
• live shorter than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• prolonged survival after rapamycin treatment
|
growth/size/body
• poor weight gain
• improved weight gain after rapamycin treatment
|
nervous system
• seizures at around 2-3 weeks of life
• occasional seizures at 3 weeks of age, earlier onset than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• become progressively more frequent over the ensuing month
• have more seizures than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• fewer seizures after rapamycin treatment
|
• gross, generalized megencephaly
• rapamycin decreases the megencephaly
|
• increased brain weight starting at 3 weeks of age
• become progressively more obvious with time
• more severe than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
|
• progressive neuronal disorganization in hippocampus with a dispersion of the pyramidal cell layer
• more severe than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• greater CA1 pyramidal cell layer width in hippocampus than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• rapamycin reduces the dispersion of the pyramidal cell layer in hippocampus
|
astrocytosis
(
J:167241
)
• progressive increase in astrocyte number diffusely throughout the brain
• most obviously in neocortex and hippocampus
• detectable as early as 1 week of life, earlier onset than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• progressively more severe beyond 3 weeks of age
• more severe than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• rapamycin decreases the proliferation of astrocytes
|
behavior/neurological
• seizures at around 2-3 weeks of life
• occasional seizures at 3 weeks of age, earlier onset than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• become progressively more frequent over the ensuing month
• have more seizures than Tsc1tm1Djk/Tsc1tm1Djk Tg(GFAP-cre)8Gtm/0 mice
• fewer seizures after rapamycin treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:167241 |